PROM, or Premature Rupture Of the Membranes surrounding the fetus (sometimes called the amniotic membrane (AM)) is a serious complication of mid to late pregnancy. PROM, and subsequent leakage of amniotic fluid, is a major precursor of premature delivery, and of concurrent infection. Prematurity and infection are in turn major causes of morbidity and mortality, and frequently lead to permanent impairment of the fetus, as well as high levels of medical expense both prepartum and postpartum.
PROM from any cause is considered here. Known causes of PROM include trauma, surgical intervention, and amniocentesis. However, PROM is primarily xe2x80x9cspontaneousxe2x80x9d, i.e., of unknown origin. It is believed that spontaneous PROM occurs most commonly near the proximal cervix, which is the locus of the highest hydrostatic pressure on the membranes, and is also the most exposed to bacterial attack. However, in most clinical cases the exact location of the rupture in spontaneous or trauma-caused PROM is not known. Such ruptures rarely self-seal.
If membrane rupture could be repaired, or if leakage of amniotic fluid could be minimized or prevented, it is believed that premature delivery could be significantly delayed, thereby significantly extending the degree of fetal maturity. Every day of extension of pregnancy can decrease the severity of fetal impairment due to prematurity by up to one percent; thus, maximizing the duration of pregnancy is clinically important. Cessation of leakage would also tend to minimize intrauterine infection. However, there are at present no reliable techniques for such treatment. In particular, the amniotic membrane is poorly vascularized and slow to heal, and is not easily accessible. Moreover, the location of the rupture is often difficult to determine.
The literature describes attempts to block amniotic fluid release by means of balloons, or with fibrin glue. Neither of these techniques has been sufficiently successful to enter general practice. Restriction of amniotic fluid loss with a balloon or similar device may be ineffective to prevent infection, and fibrin glue is typically rapidly degraded.
Materials and techniques for treating body tissues and sealing leaking lesions in tissues are known.
U.S. Pat. No. 5,410,016 (Hubbell, et al.) describes hydrogels of polymerized and crosslinked macromers comprising hydrophilic oligomers having biodegradable monomeric or oligomeric extensions. Biodegradation occurs at the linkages within the extension oligomers and results in fragments which are non-toxic and easily removed from the body. Applications for the hydrogels include adhering or sealing tissues together.
U.S. Pat. No. 5,575,815 (Slepian, et al.) describes a method for providing a synthetic barrier made of biocompatible polymeric material in vivo which involves application of a material to a tissue or cellular surface such as the interior surface of a blood vessel, tissue lumen or other hollow space. The polymeric material may also be applied to tissue contacting surfaces of implantable medical devices.
U.S. Pat. No. 5,612,050 (Rowe, et al.) describes an apparatus and method for applying an initially fluent material to a surface of a mammalian tissue including soft, living tissue and then activating the material by exposure to an energy source. The device and associated methods enable treatment of medical conditions including the application of a barrier to soft tissue to prevent post-surgical adhesions.
U.S. Pat. No. 5,800,373 (Melanson, et al.) describes a barrier or drug delivery system that is adherent to the surface to which it is applied. Tissue can be stained with a photoinitiator, then a polymer solution or gel having added thereto a defined amount of the same or a different photoinitiator can be applied to the tissue. Exposure of light causes polymerization at the surface, providing adherence and forming a gel. The resulting polymerizable barrier materials are useful for sealing tissue surfaces and junctions against leaks of fluids.
U.S. Pat. No. 5,900,245 (Sawhney, et al.) describes a barrier or drug delivery system which is adherent to the surface to which it is applied. The tissue sealant is capable of conforming to the three dimensional structure of a tissue surface as the tissue bends and deforms during healing processes.
Materials and techniques to treat Premature Rupture Of the Membranes (PROM) during pregnancy are also known.
Baumgarten and Moser, xe2x80x9cThe Technique of Fibrin Adhesion for Premature Rupture of the Membranes During Pregnancy,xe2x80x9d J. Perint. Med., 14:43-49 (1986), describe a technique of fibrin adhesion for premature rupture of membranes during pregnancy. Cerclage of the cervix is suggested prior to applying the sealant in order to prevent the fibrin clot from being flushed out prematurely by flow of amniotic fluid, as direct adhesion of the fibrin sealant to the cervical wall is not to be expected.
Uchide et al., xe2x80x9cIntracervical Fibrin Installation as an Adjuvant to Treatment for Second Trimester Rupture of Membranes,xe2x80x9d Arch. Gynecol. Obstet., 255:95-98 (1994), describe the treatment of PROM with cerclage and repeated intercervical applications of fibrin which maintain effectiveness for approximately two weeks. Leakage of amniotic fluid was not completely stopped.
Ogita et al., xe2x80x9cClinical Effectiveness of a New Cervical Indwelling Catheter in the management of Premature Rupture of the Membranes: A Japanese Collaborative Study,xe2x80x9d Am. J. Obstet. Gynecol., Vol 159, No. 2, pp336-341, (August 1988), describe the use of a cervical catheter which is fixed in the cervical canal by inflating balloons. Patients were assigned bed rest and saline and other fluids were administered daily. The delay in delivery ranged between 3 days and 2.5 weeks.
As the above references indicate, a need exists for improved methods to treat physiological conditions of pregnancy. In particular, improved methods are needed which allow the installation of a barrier serving as a partial or, preferably, complete, hydraulic seal to contain the amniotic fluid within the uterine cavity. This may be achieved by a sealing of the rupture itself, or by a sealing of the cervix to maintain the amniotic fluid in the uterus and therefore largely within the space defined by the amniotic membranes.
The present invention provides a series of techniques for conversion of fluent to non-fluent material at surfaces of physiology associated with pregnancy.
One aspect of the invention involves a method for treatment of premature rupture of the membranes of pregnancy(PROM), involving applying a fluent material to a tissue selected from at least one of an amniotic membrane, a cervix and a uterine wall, and causing the fluent material to become a non-fluent material, thereby providing an essentially complete seal which retains amniotic fluid.
In another aspect, the invention provides a device for treatment of PROM, wherein the device comprises a proximal end for manipulation of the device, a distal end for insertion into the patient""s body, and at least one lumen with an opening at the distal end of the device suitable for delivery of a fluent material to a treatment space bounded by at least one of the uterine wall, the membranes, and the proximal cervix, whereby an at least partial hydraulic seal is created in the vicinity of said space.
In another aspect, the invention involves use of a fluent material for the manufacture of a medicament for use in a method of providing therapeutic treatment to an amniotic membrane of a patient or a uterine wall or cervix of a pregnant patient, the method comprising applying the fluent material to the amniotic membrane of the patient or the uterine wall or cervix of the pregnant patient, and causing the fluent material to become non fluent.
In another aspect, the invention involves use of a fluent material for the manufacture of a medicament for use in a method of treating an amniotic membrane of a patient or a uterine wall or cervix of a pregnant patient by applying the fluent material to the amniotic membrane of the patient or the uterine wall or cervix of the pregnant patient, and causing the fluent material to become non fluent, thereby providing an essentially complete seal which retains amniotic fluid.
In another aspect, the invention involves use of a fluent material for the manufacture of a medicament for use in a method of treating at least one of the cervix, uterine wall, and amniotic membrane of a patient by accessing at least one of the cervix, uterine wall, and amniotic membrane surgically, applying a fluent material to at least one of the cervix, uterine wall and amniotic membrane, and causing the fluent material to become non fluent.
In another aspect, the invention involves use of a fluent material for the manufacture of a medicament for use in a method of treating at least one of a cervix, uterine wall and amniotic membrane of a patient by introducing a treatment device into a vagina of a patient. applying at least one of a synthetic fluent material and synthetic fluent hydrogel to at least one of a cervix, uterine wall and amniotic membrane, and causing at least one of the synthetic fluent material and synthetic fluent hydrogel to become non fluent to form a seal.
In another aspect, the invention involves use of a fluent material for the manufacture of a medicament for use in a method of treating the cervix of a patient by inserting an at least preformed plug comprising at least one of a biologically compatible polymer and a hydrogel into the cervix of a patient to form a seal.
In another aspect, the invention involves use of a fluent material for the manufacture of a medicament for use in a method of treating a treatment site of a uterine wall, amniotic membrane, or cervix of a patient percutaneously by accessing a treatment site of a uterine wall, amniotic membrane, or cervix of a patient percutaneously, and therapeutically treating the treatment site.
In another aspect, the invention involves use of a gelling material for the manufacture of a medicament for use in a method of treating premature rupture of the membranes of pregnancy (PROM) by instilling a gelling material to form a layer in a treatment space, wherein the treatment space is bounded by one or more of the amniotic membrane, the cervix and the uterine wall, and causing the material to form a hydrogel, thereby providing a hydraulic seal which retains amniotic fluid.
In another aspect, the invention involves a method including accessing at least one of the cervix, uterine wall, and amniotic membrane surgically, applying a fluent material to at least one of the cervix, uterine wall and amniotic membrane, and causing the fluent material to become non fluent.
In another aspect, the invention involves a method including introducing a treatment device into a vagina of a patient, applying at least one of a synthetic fluent material and synthetic fluent hydrogel to at least one of a cervix, uterine wall and amniotic membrane, and causing at least one of the synthetic fluent material and synthetic fluent hydrogel to become non fluent to form a seal.
In another aspect, the invention involves a method including inserting at least one of a preformed plug comprising at least one of a biologically compatible polymer and hydrogel into the cervix of a patient to form a seal.
In another aspect, the invention involves a method including inserting at least one of a sheath and tube into a vagina of a patient and placing a treatment device in at least one of the sheath and tube.
In another aspect, the invention involves a method including accessing a treatment site of a uterine wall, amniotic membrane, or cervix of a patient percutaneously, and therapeutically treating the treatment site.
In another aspect, the invention involves a method for treatment of premature rupture of the membranes of pregnancy (PROM), the method including instilling a gelling material to form a layer in a treatment space, wherein the treatment space is bounded by one or more of the amniotic membrane, the cervix and the uterine wall, and causing the material to form a hydrogel, thereby providing a hydraulic seal which retains amniotic fluid.
In another aspect the invention involves a device for treatment of PROM, wherein the device comprises a proximal end for manipulation of the device, a distal end for insertion into the patient""s body, and at least one lumen suitable for delivery of a gelling material to a treatment space bounded by two or more of the uterine wall, the membranes, and the proximal cervix.
A method involving applying a fluent material to an amniotic membrane of a patient or a uterine wall of a pregnant patient, and causing the fluent material to become nonfluent.
A method involving applying any one of a synthetic fluent material and a polysaccharide to an amniotic membrane of a patient or a uterine wall or cervix of a pregnant patient, and causing the synthetic fluent material or polysaccharide to become nonfluent.
Other advantages, novel features, and objects of the invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawing, which is schematic not intended to be drawn to scale.